Soluble CD36 Ectodomain Binds Negatively Charged Diacylglycerol Ligands and Acts as a Co-Receptor for TLR2 英文参考文献.docVIP

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Soluble CD36 Ectodomain Binds Negatively Charged Diacylglycerol Ligands and Acts as a Co-Receptor for TLR2 英文参考文献.doc

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Soluble CD36 Ectodomain Binds Negatively Charged Diacylglycerol Ligands and Acts as a Co-Receptor for TLR2 英文参考文献

SolubleCD36EctodomainBindsNegativelyCharged DiacylglycerolLigandsandActsasaCo-Receptorfor TLR2 MaximilianoJ.Jimenez-Dalmaroni1,2¤b,NengmingXiao3,AdamL.Corper2,PetraVerdino2,GaryD. Ainge4,5,DaveS.Larsen4,GavinF.Painter4,PaulineM.Rudd1¤a,RaymondA.Dwek1,KasperHoebe6*, BruceBeutler3*,IanA.Wilson2* 1Glycobiology Institute,Department of Biochemistry, University of Oxford, Oxford, United Kingdom, 2Department of Molecular Biology and the Skaggs Institute for ChemicalBiology,TheScrippsResearchInstitute,LaJolla,California,UnitedStatesofAmerica,3DepartmentofGenetics,TheScrippsResearchInstitute,LaJolla,California, UnitedStatesofAmerica,4IndustrialResearchLimited,CarbohydrateChemistry,LowerHutt,NewZealand,5UniversityofOtago,Dunedin,NewZealand,6Divisionof MolecularImmunology,CincinnatiChildren’sHospitalResearchFoundation,Cincinnati,Ohio,UnitedStatesofAmerica Abstract Background:Clusterofdifferentiation36(CD36)isatransmembraneglycoproteininvolvedinmanybiologicalprocesses, such as platelet biology, angiogenesis and in the aetiopathology of atherosclerosis and cardiovascular diseases. Toll-like receptors (TLRs) are one of the most important receptors of the innate immune system. Their main function is the recognition of conserved structure of microorganisms. This recognition triggers signaling pathways that activate transcriptionofcytokinesandco-stimulatorymoleculeswhichparticipateinthegenerationofanimmuneresponseagainst microbes.Inparticular,TLR2hasbeenshowntorecognizeabroadrangeofligands.Recently,weshowedthatCD36serves asaco-receptorforTLR2andenhancesrecognitionofspecificdiacylglyceridesderivedfrombacteria. Methodology/PrincipalFindings:Here,weinvestigatethemechanismbywhichCD36contributestoligandrecognition andactivationofTLR2signalingpathway.WeshowthattheectodomainofmurineCD36(mCD36ED)directlyinteractswith negativelychargeddiacylglycerolligands,whichexplainsthespecificityandselectivityofCD36asaTLR2co-receptor.We alsoshowthatmCD36EDamplifiesthepro-inflammatoryresponsetolipoteic